The following discussion of the prior art is provided to place the invention in an appropriate technical context and enable the advantages of it to be more fully understood. It should be appreciated, however, that any discussion of the prior art throughout the specification should not be considered as an express or implied admission that such prior art is widely known or forms part of common general knowledge in the field.
Bone, as a living tissue, has the ability to heal itself, however in some cases damage to the bone from whatever cause is too severe to allow natural healing to take place, and so a bone graft is required to stimulate regeneration. There are three main types of bone grafts: autografts, allografts and synthetic grafts. Significant research is being conducted in the field of synthetic grafts as bone substitutes since synthetic grafts can ameliorate many of the problems associated with autografts and allografts, such as limited supply, donor site pain, and immunogenicity issues.
In the case of advanced degenerative bone disease, joint replacement therapy remains the only treatment available for relieving the pain and suffering. However, the technologies available in this area of orthopaedics are far from satisfactory. For example, Australians require more than sixty-thousand hip and knee replacement operations annually, a rate that has been estimated to be increasing by some 10% per annum, and a staggering 25% of which are revisions of failed implants [Graves, S. E., et al., The Australian Orthopaedic Association National Joint Replacement Registry. Med. J. Aust., 2004; 180 (5 Suppl): p.S31-4]. Further complications arise in situations where bone stock is compromised, or where initial implant stability is questionable (e.g., elderly patients, post-traumatic injuries or in revision operations), in which cases short- and long-terms clinical results are typically inferior. The increases in life expectancy, and in the number of younger patients requiring implants, highlights the need for greater implant longevity and has driven biomedical research to develop novel micro-engineered surfaces to anchor the cementless prosthesis directly to the living bone through osteo-integration, thereby attempting to provide a stable interface strong enough to support life-long functional loading. It is clear that there is a serious problem with the longevity of current orthopaedic devices; a problem that is anticipated to only increase with the increasing demand from the aging population requiring such treatments. It is clear that any improvement that could be made to increase the performance of these orthopaedic devices would be welcomed, not only by the orthopaedic community but also by the patients themselves.
3D scaffolds that promote the migration, proliferation and differentiation of bone and endothelial cells are becoming increasingly important in not only orthopaedic but also maxillofacial surgery. An ideal bone replacement material should support bone formation and vascularisation; show minimal fibrotic reaction and serve as a temporary biomaterial for bone remodeling. They must also degrade in a controlled fashion into non-toxic products that the body can metabolise or excrete via normal physiological mechanisms (Yaszemski, et al., Biomaterials, 1996, 17, pp. 175-185). Scaffolds need to be mechanically strong and matched with a similar modulus of elasticity to that of bone in order to prevent stress shielding as well as maintaining adequate toughness to prevent fatigue fracture under cyclic loading. At present there are no successful strategies available for bone tissue regeneration and resurfacing arthritic joints with articular cartilage. The lack of cartilage reparative response creates a great demand for new modalities that promote tissue regeneration.
Over the last century, various ceramics have been investigated for the purpose of encouraging or stimulating bone growth and as scaffolds. For example, in the 1880s calcium sulfate (plaster of Paris) was utilised. However, calcium sulfate displays a relatively low bioactivity and a relatively high rate of degradation (Tay, et al., Orthop. Clin. North Am., 1999, 30:615-23). In the 1950s hydroxyapatite was utilised, but it suffers from a relatively low degradation rate and poor mechanical properties (Wiltfang J., et al J. Biomed. Mater. Res. 2002;63:115-21). In the 1970s Bioglass® was developed. However, this material it is relatively hard to handle due to its inherent brittleness and has a relatively low bending strength (Cordioli G., Clin. Oral Implants Res. 2001, 13:655-65). In the 1990s calcium silicate ceramics began being used for stimulating bone growth. They are regarded as potential bio active materials and their degradation products do not incite an inflammatory reaction. However, drawbacks exist with these materials that compromise their physical and biological properties including their a.) inability to combine the required mechanical properties with open porosity b.) poor mechanical strength making them unsuitable for load-bearing applications; and c.) poor chemical instability (high degradation rate) leading to a highly alkaline condition in the surrounding environment which is detrimental to cell viability and limits their long-term biological applications.
Whilst other more recent ceramics such as HAp, Bioverit®, Ceraverit® and other calcium silicates have been found to bond to living bone and meet wide clinical applications, i.e., good bioactivity, they cannot be used in highly loaded areas, such as the cortical bone found in, for example, legs, due to the relative brittleness of these materials. Thus the materials possess good bioactivity, but lack full biodegradability after implantation and their mechanical strength is compromised [Hench L. L., J Am Ceram. Soc. 1998 81: 1705-28]. They are too brittle and fracture frequently. For at least this reason such materials typically find their use limited to coatings on metallic implants.
Another known material is doped Hardystonite, as detailed in International Publication No. WO 2010/003191. Doped Hardystonite is a biocompatible ceramic material comprising Sr, Mg or Ba doped Hardystonite (Ca2ZnSi2O7).
It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the above mentioned prior art, or to provide a useful alternative.
It is an object of an especially preferred form of the present invention to provide for a composite biocompatible ceramic material that may be useful for improving the long term stability of, for instance, an implantable medical device and/or an implantable drug delivery device comprising such a material.
Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.
Although the invention will be described with reference to specific examples it will be appreciated by those skilled in the art that the invention may be embodied in many other forms.
The skilled person will appreciate that the term “biocompatible” defines a two-way response, i.e., the body's response to the material and the material's response to the body. The biocompatibility of a medical device refers to the ability of the device to perform its intended function, with the desired degree of incorporation in the host, without eliciting any significant or long-term undesirable local or systemic effects in that host.